title: Endothelial colony-forming cells derived from pregnancies complicated by intrauterine growth restriction are fewer and have reduced vasculogenic capacity.
abstract: BACKGROUND
  Endothelial colony-forming cells (ECFCs) are the only putative endothelial progenitor cells capable of vasculogenesis, and their dysfunction may represent a risk factor for cardiovascular disease. Intrauterine growth restriction (IUGR) is a pregnancy-related disorder associated with long-term cardiovascular risk.
  
  
  OBJECTIVE
  Our objective was to determine whether ECFCs derived from pregnancies complicated by IUGR exhibit altered vasculogenic potential.
  
  
  METHODS
  This was a prospective cohort study; patients were recruited at St. Mary's Hospital, Manchester, United Kingdom.
  
  
  METHODS
  Twenty-three women with normal pregnancies and 13 women with IUGR-complicated pregnancies at gestational ages above 37 weeks were included.
  
  
  METHODS
  Vasculogenic capacity of rigorously characterized ECFCs was investigated in vivo by measuring blood vessel formation in collagen/fibronectin gels implanted in mice; proliferative, migratory, and chemotactic abilities were assessed in cell culture. Placental uptake of fetal ECFCs, assessed by differences in arterial and venous cord blood content, was determined by flow cytometry.
  
  
  RESULTS
  In vivo, IUGR ECFCs formed fewer blood vessels (P < .001) and capillaries (P = .001) compared with normal pregnancy-derived ECFCs. In culture conditions, IUGR ECFCs had reduced proliferation (P = .01) and migration (P = .007) and diminished chemotactic abilities to stromal cell-derived factor 1 (P = .007) coupled with reduced hypoxia-induced matrix metalloproteinase-2 release (P = .02). Finally, in IUGR pregnancies, the number of ECFCs was lower in arterial cord blood (P = .002) and placental uptake of cells was reduced (P < .001).
  
  
  CONCLUSIONS
  ECFCs derived from IUGR cord blood are rarefied and dysfunctional, resulting in diminished vasculogenic potential; this could be a cause of placental dysfunction in IUGR, with long-term postnatal implications for cardiovascular function in offspring.
authors.affiliation: Maternal and Fetal Health Research Centre, Manchester Academic Health Science Centre, University of Manchester, Central Manchester University Hospitals National Health Service Foundation Trust, Oxford Road, Manchester M13 9WL, United Kingdom. Ian.crocker@manchester.ac.uk.
authors.forename: Peter I
authors.initials: PI
authors.lastname: Sipos
authors.forename: Stephane L
authors.initials: SL
authors.lastname: Bourque
authors.forename: Carl A
authors.initials: CA
authors.lastname: Hubel
authors.forename: Philip N
authors.initials: PN
authors.lastname: Baker
authors.forename: Colin P
authors.initials: CP
authors.lastname: Sibley
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
authors.forename: Ian P
authors.initials: IP
authors.lastname: Crocker
mesh_terms: D002196:Capillaries / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology; D002452:Cell Count; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D015331:Cohort Studies; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005312:Fetal Blood; D005317:Fetal Growth Retardation / Q000097:blood / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D053686:Fetal Stem Cells / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D010920:Placenta / Q000098:blood supply / Q000473:pathology; D011247:Pregnancy; D011446:Prospective Studies
chemical_list: C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2